Reflecting on more than two decades of the ELSI "experiment"

By Steven Benowitz
Associate Director of Communications, Extramural Research Program

At its heart, ELSI - the Ethical, Legal and Social Implications Program at the National Human Genome Research Institute (NHGRI) - remains an experiment. As the largest extramural research program in bioethics at the National Institutes of Health, ELSI funds more studies on ethical, legal and social issues related to genomics and genetics than any other program in the country. Yet this seeming contradiction - a science ethics program that is also a part of the same agency that funds the science underlying genomics research - is also an opportunity for ELSI grantees and genomics researchers to work as partners.

The ELSI Research Program, established in 1990 and later sanctioned by an act of Congress, is seen by some as the de facto conscience of genomic research and medicine. In reality, the ELSI Program is much more. In the genomics universe, the term "ELSI" - or perhaps even more broadly, "ELSI issues" - is used almost generically now to refer to matters at the intersection of genomics and society. ELSI projects explore a wide range of topics, from the ethical and legal issues raised by genomic biobanks and biorepositories (which may contain large volumes of patient information, including DNA samples) to ethical concerns related to genomic information in the prenatal or newborn setting.

Writing online recently in the Annual Review of Genomics and Human Genetics, some of the long-term leaders of the program reflected on more than two decades of ELSI's existence.

"ELSI was first launched at the beginning of the Human Genome Project, almost as an afterthought," noted co-author Jean McEwen, J.D., Ph.D., ELSI program director at NHGRI.

Yet early on, some, including Nobel Laureate James Watson, Ph.D., understood that future discoveries and technologies would raise important ethical implications. Dr. Watson, the initial director of NHGRI's predecessor, the National Center for Human Genome Research (NCHGR), and the first director of the NIH Human Genome Project, advocated for a program to examine these issues. In 1993, Congress established NCHGR and mandated that "not less than 5 percent of the NIH Human Genome Project budget be set aside for research on the ethical, legal and social implications of genomic science."

"Dr. Watson and many others realized that there would be extraordinarily difficult and sometimes perplexing issues to deal with," Dr. McEwen said. "In the beginning, the program had somewhat of a public education mission, and a think-tank feel to it. We had to figure out how we could anticipate ethical issues before they actually came up. This had never been done before in a systematic way in science. It was really launched as an experiment, and it continues that way today."

"Gradually, we realized that research needed to be done to understand and try to find solutions and establish guidelines for issues surrounding genomics, and slowly it evolved to today where it is fundamentally a research program," she said. "While ELSI research tackles the immediate issues that arise in research labs and the clinic, but it's also looking at the downstream implications of situations in society and how genomics will affect peoples' lives."

The program's initial budget of $1.57 million in fiscal year (FY) 1990 grew to $18 million in FY2013. The program has awarded nearly $317 million in research support and funded more than 480 projects. While most of the projects are initiated by investigators, owing to the program's goal of "intellectual independence," many important projects are part of larger programs.

One of those programs is the Centers of Excellence in ELSI Research (CEER), which was established in 2004. CEERs bring together experts in bioethics, law, behavioral and social sciences, clinical research, theology, public policy, and genetic and genomic research to develop innovative, interdisciplinary approaches related to genomics. Recently funded CEER teams are investigating such topics as how families respond to information about their future children's genetic risks and the impact of providing information on the genomics of psychiatric conditions on individuals' self-image and on societal stigma. While stand-alone research grants have been the traditional core of ELSI-supported research, a more recent trend finds ELSI projects embedded within existing, extramural-funded research programs. These include the Clinical Sequencing Exploratory Research program, the Electronic Medical Records and Genomics Network, and more. Grant applications for these programs are required to include a component that examines the ELSI issues arising from the research.

"By integrating ELSI research into existing programs, scientists are conducting research in conjunction with the ongoing project," Dr. McEwen said. "This approach really took off with the advent of genomic medicine. We decided that we should be studying these issues in the clinic in real time as these situations are happening."

The authors describe how the ELSI Research Program has informed and shaped polices related to the use of genomic information in the clinic. Some of the early ELSI-funded studies examined ethical and social issues related to screening populations, carrier testing, prenatal testing and newborn screening. More recently, new technologies increasingly allow researchers to sequence the entire genomes or the complete protein-coding sections of genomes of patients. In response, new ELSI projects are probing the often controversial question of what to do with unintended, "incidental" findings that were not the main focus of the study, but could have a potential impact on a person's health.

ELSI's impact

As ELSI's make-up changes with the times, so does its impact.

"ELSI has made its greatest mark to date in ways genomics research is conducted," said Dr. McEwen, explaining that genomics has only recently begun to be introduced as part of patient care.

ELSI research also has helped foster new approaches to informed consent - an agreement to make sure that an individual is aware of the potential risks and benefits of participating in genomics and genetics research. The ELSI program also played a role in developing national guidelines for widely sharing data generated from human subjects research. These include issues related to study participant privacy and the use of large repositories of patient information, including DNA samples.

The authors noted that ELSI research has also affected how the interests of certain groups are taken into account in genomics research. They point to the International HapMap Project and the 1000 Genomes Project as examples of programs that examined genetic variation in ethnically diverse populations.

"Researchers want to avoid potential minefields in these studies that examine the complex relationship between genetics and race and ethnicity. They appreciate having input from those trained in areas such as anthropology and social sciences to help address questions like how we label populations in scientifically valid ways that are sensitive to the unique cultural concerns of communities," Dr. McEwen explained.

Many ELSI issues are interconnected. Privacy issues affect what and how much information may be addressed in a consent form and the ground rules for sharing data. Privacy is also connected to genetic discrimination - another area on which ELSI research has had an impact - and which helped lead to the passage of the Genetic Information Nondiscrimination Act (GINA) in 2008.

The authors suggested that scientists increasingly seem to appreciate the value that ELSI research contributes to their own work. They emphasized the importance of raising awareness in the public about such issues, and said that ELSI studies have affected public perception, though the program's impact in this area is difficult to quantify.

"People realize genetics and genomics are not the only factors in determining a person's likelihood to develop a disease as perhaps once envisioned," Dr. McEwen said. "ELSI work has had an impact on a wide range of groups, from scientists and policy makers to reporters and the public. It's a challenge to keep up and stay one step ahead of the science and try to anticipate the newest questions."